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Myelodysplastic syndromes: advantages of a combined cytogenetic and molecular diagnostic workup

In this study we present a new diagnostic workup for the myelodysplastic syndromes (MDS) including FISH, aCGH, and somatic mutation assays in addition to the conventional cytogenetics (CC). We analyzed 61 patients by CC, FISH for chromosome 5, 7, 8 and PDGFR rearrangements, aCGH, and PCR for ASXL1,...

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Autores principales: Ciabatti, Elena, Valetto, Angelo, Bertini, Veronica, Ferreri, Maria Immacolata, Guazzelli, Alice, Grassi, Susanna, Guerrini, Francesca, Petrini, Iacopo, Metelli, Maria Rita, Caligo, Maria Adelaide, Rossi, Simona, Galimberti, Sara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668031/
https://www.ncbi.nlm.nih.gov/pubmed/29108298
http://dx.doi.org/10.18632/oncotarget.16578
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author Ciabatti, Elena
Valetto, Angelo
Bertini, Veronica
Ferreri, Maria Immacolata
Guazzelli, Alice
Grassi, Susanna
Guerrini, Francesca
Petrini, Iacopo
Metelli, Maria Rita
Caligo, Maria Adelaide
Rossi, Simona
Galimberti, Sara
author_facet Ciabatti, Elena
Valetto, Angelo
Bertini, Veronica
Ferreri, Maria Immacolata
Guazzelli, Alice
Grassi, Susanna
Guerrini, Francesca
Petrini, Iacopo
Metelli, Maria Rita
Caligo, Maria Adelaide
Rossi, Simona
Galimberti, Sara
author_sort Ciabatti, Elena
collection PubMed
description In this study we present a new diagnostic workup for the myelodysplastic syndromes (MDS) including FISH, aCGH, and somatic mutation assays in addition to the conventional cytogenetics (CC). We analyzed 61 patients by CC, FISH for chromosome 5, 7, 8 and PDGFR rearrangements, aCGH, and PCR for ASXL1, EZH2, TP53, TET2, RUNX1, DNMT3A, SF3B1 somatic mutations. Moreover, we quantified WT1 and RPS14 gene expression levels, in order to find their possible adjunctive value and their possible clinical impact. CC analysis showed 32% of patients with at least one aberration. FISH analysis detected chromosomal aberrations in 24% of patients and recovered 5 cases (13.5%) at normal karyotype (two 5q- syndromes, one del(7) case, two cases with PDGFR rearrangement). The aGCH detected 10 “new” unbalanced cases in respect of the CC, including one with alteration of the ETV6 gene. After mutational analysis, 33 patients (54%) presented at least one mutation and represented the only marker of clonality in 36% of all patients. The statistical analysis confirmed the prognostic role of CC either on overall or on progression-free-survival. In addition, deletions detected by aCGH and WT1 over-expression negatively conditioned survival. In conclusion, our work showed that 1) the addition of FISH (at least for chr. 5 and 7) can improve the definition of the risk score; 2) mutational analysis, especially for the TP53 and SF3B1, could better define the type of MDS and represent a “clinical warning”; 3) the aCGH use could be probably applied to selected cases (with suboptimal response or failure).
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spelling pubmed-56680312017-11-04 Myelodysplastic syndromes: advantages of a combined cytogenetic and molecular diagnostic workup Ciabatti, Elena Valetto, Angelo Bertini, Veronica Ferreri, Maria Immacolata Guazzelli, Alice Grassi, Susanna Guerrini, Francesca Petrini, Iacopo Metelli, Maria Rita Caligo, Maria Adelaide Rossi, Simona Galimberti, Sara Oncotarget Clinical Research Paper In this study we present a new diagnostic workup for the myelodysplastic syndromes (MDS) including FISH, aCGH, and somatic mutation assays in addition to the conventional cytogenetics (CC). We analyzed 61 patients by CC, FISH for chromosome 5, 7, 8 and PDGFR rearrangements, aCGH, and PCR for ASXL1, EZH2, TP53, TET2, RUNX1, DNMT3A, SF3B1 somatic mutations. Moreover, we quantified WT1 and RPS14 gene expression levels, in order to find their possible adjunctive value and their possible clinical impact. CC analysis showed 32% of patients with at least one aberration. FISH analysis detected chromosomal aberrations in 24% of patients and recovered 5 cases (13.5%) at normal karyotype (two 5q- syndromes, one del(7) case, two cases with PDGFR rearrangement). The aGCH detected 10 “new” unbalanced cases in respect of the CC, including one with alteration of the ETV6 gene. After mutational analysis, 33 patients (54%) presented at least one mutation and represented the only marker of clonality in 36% of all patients. The statistical analysis confirmed the prognostic role of CC either on overall or on progression-free-survival. In addition, deletions detected by aCGH and WT1 over-expression negatively conditioned survival. In conclusion, our work showed that 1) the addition of FISH (at least for chr. 5 and 7) can improve the definition of the risk score; 2) mutational analysis, especially for the TP53 and SF3B1, could better define the type of MDS and represent a “clinical warning”; 3) the aCGH use could be probably applied to selected cases (with suboptimal response or failure). Impact Journals LLC 2017-03-25 /pmc/articles/PMC5668031/ /pubmed/29108298 http://dx.doi.org/10.18632/oncotarget.16578 Text en Copyright: © 2017 Ciabatti et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Clinical Research Paper
Ciabatti, Elena
Valetto, Angelo
Bertini, Veronica
Ferreri, Maria Immacolata
Guazzelli, Alice
Grassi, Susanna
Guerrini, Francesca
Petrini, Iacopo
Metelli, Maria Rita
Caligo, Maria Adelaide
Rossi, Simona
Galimberti, Sara
Myelodysplastic syndromes: advantages of a combined cytogenetic and molecular diagnostic workup
title Myelodysplastic syndromes: advantages of a combined cytogenetic and molecular diagnostic workup
title_full Myelodysplastic syndromes: advantages of a combined cytogenetic and molecular diagnostic workup
title_fullStr Myelodysplastic syndromes: advantages of a combined cytogenetic and molecular diagnostic workup
title_full_unstemmed Myelodysplastic syndromes: advantages of a combined cytogenetic and molecular diagnostic workup
title_short Myelodysplastic syndromes: advantages of a combined cytogenetic and molecular diagnostic workup
title_sort myelodysplastic syndromes: advantages of a combined cytogenetic and molecular diagnostic workup
topic Clinical Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668031/
https://www.ncbi.nlm.nih.gov/pubmed/29108298
http://dx.doi.org/10.18632/oncotarget.16578
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